About our project
Motivation and aim of this project
Metastatic prostate cancer patients often have most of their disease in bone metastases, making it hard to obtain biomaterials for analysis. Moreover, tracking the volume of disease in response to treatment is difficult as bone lesions are difficult to measure. We aim to use circulating biomarkers to probe the biology of individual tumors and to trace the response to treatment more accurately.
Execution and collaboration of this project
We collect blood samples from prostate cancer patients with their corresponding clinical data in a longitudinal fashion. We now have a biobank of specimens that may be used for research purposes. Moreover, we have started a project to perform Diagnostic Leukapheresis in prostate cancer patients to obtain enough cells for biologic research.
Funding of this project
This project has been funded by different sources. We have obtained high risk funding from the Dutch Cancer Foundation (KWF). And a recent grant has been granted from the NWO/KWF for a collaboration with the University of Twente on single cell phenotyping obtained using Diagnostic Leukapheresis.
Possible impact on patient careThe use of circulating biomarkers will allow us to repeatedly probe the disease biology in patients that are actively being treated. In fact the main problem in the treatment of cancer is the fact that we develop novel treatments that all induce their own resistance. Therefore understanding how tumors adapt to the selective pressure of treatment is crucial in improving treatment outcomes.
Our research focus
Assessing response to treatment in prostate cancer patients
In prostate cancer the difficulty in measuring response is mainly related to the fact that bone lesions cannot be measured reliably. Clinically, we use PSA to follow disease whereas we know this becomes less reliable after the first Androgen Deprivation Treatment. Improving the response evaluation may lead to more effective treatment as we can more adequately detect to treatment success and failures.
Importance of “phenotyping” prostate cancerProstate cancer cell lines are scarce and the community of prostate cancer researchers has invested considerable efforts into generating novel cell lines without much success. In our efforts to generate knowledge on how specific subgroups of patients respond to treatment we need more means to test prostate cancer cell behavior outside of patients. Circulating tumor cells may be an appropriate surrogate if we can obtain enough of them.
Funds & Grants
- Dutch Cancer Foundation (KWF)
- NWO/KWF call on technology development
Inside Erasmus MC
- Department of Urology
- Center for Computational Biology
Outside Erasmus MC
- University of Twente
- Belderbos BPS, Sieuwerts AM, Hoop EO, Mostert B, Kraan J, Hamberg P, Van MN, Beaufort CM, Onstenk W, van Soest RJ, Martens J, Sleijfer S, de Wit R, Mathijssen RHJ, Lolkema MP. Associations between AR-V7 status in circulating tumour cells, circulating tumour cell count and survival in men with metastatic castration-resistant prostate cancer. Eur J Cancer. 2019 Nov;121:48-54.
- Sieuwerts AM, Mostert B, van der Vlugt-Daane M, Kraan J, Beaufort CM, Van M, Prager WJC, De Laere B, Beije N, Hamberg P, Westgeest HM, Tascilar M, Dirix LY, Onstenk W, de Wit R, Lolkema MP, Mathijssen RHJ, Martens JWM, Sleijfer S. An In-Depth Evaluation of the Validity and Logistics Surrounding the Testing of AR-V7 mRNA Expression in Circulating Tumor Cells. J Mol Diagn. 2018 May;20(3):316-325.
- van Dessel LF, Beije N, Helmijr JC, Vitale SR, Kraan J, Look MP, de Wit R, Sleijfer S, Jansen MP, Martens JW, Lolkema MP. Application of circulating tumor DNA in prospective clinical oncology trials - standardization of preanalytical conditions. Mol Oncol. 2017 Mar;11(3):295-304.
- Onstenk W, Sieuwerts AM, Kraan J, Van M, Nieuweboer AJ, Mathijssen RH, Hamberg P, Meulenbeld HJ, De Laere B, Dirix LY, van Soest RJ, Lolkema MP, Martens JW, van Weerden WM, Jenster GW, Foekens JA, de Wit R, Sleijfer S. Efficacy of Cabazitaxel in Castration-resistant Prostate Cancer Is Independent of the Presence of AR-V7 in Circulating Tumor Cells. Eur Urol. 2015 Dec;68(6):939-45.
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